ibs-d and evaluation of chronic diarrhea · 2019-04-22 · •cost-effective evaluation and...

4/22/2019

1

©2018 MFMER | slide-1

IBS-D and Evaluation of Chronic DiarrheaAmy Foxx-Orenstein, DO, MACP, FACPProfessor of MedicineDivision of Gastroenterology and HepatologyMayo Clinic

AOMA 97th Annual Convention


No Disclosures

4/22/2019

2


IBS-D Outline

• Evidence-based criteria to evaluate patients with IBS symptoms

• Cost-effective evaluation and treatment

• Traditional and newer treatments for patients with IBS-D


Representative Case

• 35 year old female with 8 years of abdominal cramping, bloating and diarrhea on most days. No bloody stools or nocturnal episodes. Has 3-4 loose stools daily with urgency, yet never had an ‘accident’. LLQ cramping is relieved with movements. Has hypothyroidism and anxiety, on treatment. Weight is stable. No family history of IBD or colon cancer/polyps.

• Does she have IBS?• Are there other diagnosis to consider?• What tests would you do to evaluate cause?

4/22/2019

3


What Else Could It Be?Differential for diarrhea is broad and the history will divulge many clues

• Infectious

• Post-infectious

• Medication

• Bile acid

• Microscopic colitis

• Celiac

• Caffeine

• SIBO

• IBD

• Disaccharidase deficiency

• Food related

• Villous adenoma

• Toxins


Recurrent abdominal pain, on average, ≥1 day per week in the last 3 months, associated with ≥ 2 of the following:

• Related to defecation

• Change in frequency of stool

• Change in form (appearance) of stool

Rome IV Criteria for IBS

Bristol Stool Form Scale

Criteria should be fulfilled for the last 3 months with

symptom onset ≥ 6 months before diagnosis

Lacy BE et al. Gastroenterology. 2016;150:1393-1407

IBS-D IBS-M

4/22/2019

4


Diagnostic Testing for IBS-D and IBS-M symptoms

IBS-DIBS-DIBS-D IBS-MIBS-MIBS-M

•CRP, fecal calprotectin

• IgA ttG ± quantitative IgA

•Colonoscopy with random biopsies and TI exam if appropriate

•Consider EGD with small bowel biopsies

•CRP, fecal calprotectin

• IgA ttG ± quantitative IgA

CRP = C-reactive proteinttg = tissue transglutaminase.

Chey WD, et al. JAMA. 2015;313:949

Limited testing


Prevalence of Structural Abnormalities in IBS Patients Compared with Controls

7.7

0.4 1.5

26.1

00

5

10

15

20

25

30

Microscopic colitis more common in IBS-D patients

aged ≥45 years

Pat

ient

s, %

IBS patients (n=466) Controls (n=451)

Adenomas IBD Microscopic colitis

N/A

Chey WD et al. Am J Gastroenterol. 2010;105:859

Limited testing

4/22/2019

5


• Onset of symptoms after age 50

• GI bleeding or iron-deficiency anemia

• Nocturnal diarrhea

• Unintended weight loss

• Family history of organic GI disease (colorectal cancer, IBD, celiac)

Alarm Features

Proceed with testing


Celiac is Common in IBS Patients with Diarrhea

Prevalence of biopsy-proven celiac disease in IBS-D vs controls

4.34 (1.78-10.58)

International meta-analysisFord et al. Archives Int Med. 2009;169:651

4/22/2019

6


IBS and Wheat

• Most IBS patients have

wheat sensitivity,

Not celiac disease!

Leonard MM et al. JAMA. 2017;318:647Talley NJ. JAMA Intern Med. 2017;177:615


Breath Testing in IBS

Carbohdrateload

Colonic fermentation

H2 and/or methane

• Tests for CHO maldigestion and SIBO

• Conditions associated with bloating

• Heterogeneity in test performance, preparation, indications, and interpretation of results

Rezaie A et al. Am J Gastroenterol. 2017;112(775

CHO = carbohydrateSIBO = small intestinal bacterial overgrowth

4/22/2019

7


Food and IBS Symptoms

69 6458 54

0

20

40

60

80

100P

atie

nts,

%

Small meals Avoiding fat Increasingfiber

Avoiding milk products

IBS Patients Reporting Symptom ImprovementWith Intervention

(N=1,242)

60% of patients report worsening of symptoms after meals

Simren M et al. Digestion. 2001;63:108Halpert et al. Am J Gastroenterol. 2007; 102:1972


Food and IBS Symptoms: Restriction Diets

• FODMAPS are an important trigger of meal-related symptoms in IBS

• Gluten-free diet found to be beneficial in some patients with IBS-D

• Wheat contains fructans and other proteins that may also cause symptoms in IBS patients

• Food antigens may cause changes in the intestinal mucosa of IBS patients

Shepherd SJ et al. Am J Gastroenterol. 2013;108:707;Biesiekierski JR et al. Gastroenterology. 2011;106:508;Vazquez-Roque MI et al. Gastroenterology. 2013;144:903;Chey WD, et al. JAMA. 2015;313:949

4/22/2019

8


Low FODMAP vs mNICE Diet:Adequate Relief

41

52

0

10

20

30

40

50

60

Proportion of patients that answered “Yes” for ≥50% of weeks 3 and 4

N=45

mNICE Low FODMAP

N=38

Pat

ien

ts w

ith

A

deq

uat

e R

elie

f, %

P=0.3055

“In the last week, have you had adequate relief of your GI symptoms?”

mNICE, modified National Institute for Health and Care Excellence. Patients were instructed to eat small frequent meals, avoid trigger foods, and avoid excess alcohol and caffeine

Eswaran SL, et al. Am J Gastroenterol. 2016;111:1824-1832.


mNICE vs FODMAPWeekly Pain and Bloating Scores

○

§§

§

1

2

3

4

5

6

Baseline Week 1 Week 2 Week 3 Week 4

Ave

rag

e D

aily

Ab

do

min

al P

ain

S

core

s (0

-10)

m-NICE Low FODMAP

#

§§

§

1

2

3

4

5

6

Baseline Week 1 Week 2 Week 3 Week 4

Ave

rag

e D

aily

Ab

do

min

al

Blo

atin

g S

core

(0-

10)

m-NICE Low FODMAP

Abdominal Pain Scores Bloating Scores

mNICE, modified National Institute for Health and Care Excellence. Patients were instructed to eat small frequent meals, avoid trigger foods, and avoid excess alcohol and caffeine

Eswaran SL, et al. Am J Gastroenterol. 2016;111:1824-1832.

4/22/2019

9


Overview of IBS-D Therapies: MOA*

• Modulation of gut flora• Antibiotics, Probiotics, gastric acidity, diet

• 5-HT3 antagonists• Alosetron

• Antidepressants/antianxiety agents• TCA’s, SSRI’s

• Opioid receptor modulators• Loperamide, diphenoxylate, Eluxadoline

• Antispasmodics/Peppermint Oil

• Bile acid binding agents• Colestid, Cholestyramine

*MOA = Mechanisms of action


Loperamide and Antispasmodics for IBS

Loperamide

Antispasmodics Clinical trials

Patients treated

23

2,154

Clinical trials

Patients treated

2

42

Recommendation

Strong*

Quality of evidence

Very LowRecommendation

Weak

Quality of evidence

Low

Ford AC, et al. Am J Gastroenterol. 2014;109:S2-S26

*FOR DIARRHEA

4/22/2019

10


Probiotics for IBS

Clinical trials Patients treatedRecommendation

WeakQuality of evidence

LowRecommendations regarding individual species, preparations, or strains cannot be made because of insufficient and conflicting data

23 2,575



Alosetron for IBS-D

• Dose• .5-1 mg BID• Females• Not first line treatment

Alosetron is effective in

females with IBS-D

Recommendation

Strong

Quality of evidence

High

Ischemic colitis0.95 cases/1000 patient-years

Difficult constipation0.36 cases/1000 patient-years

Rare Adverse EffectsAssociated with Alosetron


4/22/2019

11


Rifaximin for IBS-D

TARGET 1 TARGET 2 Combined

40.8 40.6 40.731.2 32.2 31.7

0

20

40

60

80

100

Pat

ient

s, %

P=0.01P=0.03 P<0.001

Adequate Relief of Global* IBS Symptoms

Rifaximin Placebo

3336.9

25 29.3

0

20

40

60

80

100

Pat

ient

s, %

First repeat treatment

Second repeat treatment

P=0.04P=0.02

First and Second Retreatments

Urgency, bloating, pain, stool consistency

Pimentel M, et al. N Engl J Med. 2011;364:22


Rifaximin

• 550 mg TID 2 weeks

• Recurrence of symptoms can be retreated up to two times, same regimen

Schoenfeld P, et al. Aliment Pharmacol Ther. 2014;39:1161

4/22/2019

12


Antidepressent Agents in IBS-D

• Meta-analysis 16 RCT TCA and SSRI reduced global pain and IBS symptoms

• SSRI’s may increase intestinal transit

• SNRI’s have not been adequately studied

Antidepressant actions in IBS

Antidepressant action

Visceral analgesia

Changes in motility

Smooth muscle relaxation

Ford AC et al. Am J Gastroenterol. 2014;109:1350;Grover M, et al Gastroenterol Clin N Am. 2011;40:183;Chey WD, et al. Gut Liver. 2011;5:253;Gorard DA, et al. Aliment Pharmacol Ther. 1994;8:159


Prescribing Antidepressants in IBS

Consider specific symptoms

TCA’s in IBS-D

SSRI for anxiety

Consider Side Effects

TCA’s → constipation

SSRI → diarrhea

Start LOW dose and titrate

8 weeks for full response

6-12 months treatment

Sobin WH et al. Am J Gastroenterol. 2017;112:693;Grover M et al. Gastroenterol Clin N Am. 2011;40:183;Dekel R et al. Expert Opin Invest Drugs. 2013;22:329

4/22/2019

13


Eluxadoline for IBS-D

Placebo BID Eluxadoline 75 mg BID Eluxadoline 100 mg BID

0

20

40

60

80

100

0

20

40

60

80

100

P<0.001

Weeks 1–26Weeks 1–12

Res

po

nd

ers,

%

P<0.001

P<0.001

P<0.001

Reduced abdominal pain > 30% compared to baseline and stool consistency < 5/d daily, for >50% of days in trial

Lembo AJ, et al. N Engl J Med. 2016;374:242

Mixed opioid receptor agonist (mu) and antagonist (delta)


Eluxadoline Adverse Events

Sphincter of Oddispasm events 0.6% (10 /1666) In patients who did not have gall bladders

PancreatitisAlcohol use and biliary sludge increase risk

AdverseEvents

Placebo (n=808)

Eluxadoline75 mg

(n=859)

Eluxadoline100 mg (n=807)

n (%)

Constipation* 20 (2.5) 60 (7.4) 74 (8.6)

Nausea 41 (5.1) 65 (8.1) 64 (7.5)

Abdominal pain† 33 (4.0) 47 (5.9) 62 (7.2)

Vomiting 11 (1.4) 32 (4.0) 36 (4.2)

Gastroenteritis‡ 27 (3.4) 36 (4.4) 19 (2.2)

URI 32 (4.0) 27 (3.3) 47 (5.5)

Nasopharyngitis 27 (3.3) 33 (4.1) 23 (2.7)

4/22/2019

14


Prescribing Eluxadoline

• 100 mg BID with food

• 75 mg BID for patients with hepatic impairment

Contraindications

1. Bile duct disorders

2. NO Gallbladder

3. History of pancreatitis

4. Severe constipation or liver disease

5. ETOH daily


Peppermint Oil for IBS

• Improved total IBS symptom score, frequency and intensity of symptoms over 4 weeks (p<0.02)

• Adverse events: dyspepsia

• Prescribing PPO• 180 mg tid

0

20

40

60

80

100

AbdominalPain or

Discomfort

AbdominalBloating orDistension

Pain atEvacuation

Sym

pto

m r

edu

ctio

n, %

Placebo TID(n=37)

Peppermint oil 180 mg TID (n=35)

Cash BD, et al. Dig Dis Sci. 2016;61:560

4/22/2019

15


Psychological Therapy is Effective in Many Patients With IBS

• 20 studies• Mindfulness, cognitive behavioral therapy, psychotherapy,

hypnosis

Psychological therapy

(%)

Control therapy

(%)RR symptoms remain

(95% CI)

49.1 27.5 0.67(0.57-0.79)

Ford AC et al. BMJ. 2008;337:a2313.Walter SA et al. Neurogastroenterol Motil 2013;25:741.Halland M, Talley NJ. Nat Rev Gastroenterol Hepatol 2013;10:13.

Patients often respond to psychological support, including strong physician-patient relationship

N=1278


Exercise Has a Positive Impact on IBS Symptoms

• Randomized to physical activity* or maintain lifestyle

• Control group had significantly higher IBS symptom scores than patients in physical activity group

• Physical activity improvedIBS symptom scores (p=0.003)

Johannesson E et al. Am J Gastroenterol. 2011;106:915-922.

500

400

300

200

100

0

IBS

Sev

erit

y S

core

Control group Physical activity group

P = 0.001

Start 12 Weeks

*Intervention: 20-60 minutes moderate to vigorous exercise 3-5 times weekly

(N=75)

4/22/2019

16


Summary IBS-D

• Diagnose using symptom-based criteria

• Check TTG, CRP• Consider referral for endoscopy, breath tests

• Educate• Primary role of diet in managing IBS

• Smaller meals, FODMAP, elimination • Medications to achieve a goal: reduce pain and

diarrhea, improve quality of life

• Psychological therapy

• Exercise


The End

But there’s more…

4/22/2019

17


Evaluation and Management of Chronic Diarrhea (not IBS)


Outline

• Stepwise approach to diagnosis and management of chronic diarrhea

• Features of chronic diarrhea that warrant an evaluation

• When and what tests are warranted

4/22/2019

18


Representative Case

• 53 y/o woman with diarrhea for 2 years. She has 4-6 watery stools daily, no formed stool. No blood, but she has nocturnal stools, cramps and bloating. Medical history of hypothyroidism and depression (treated). Underwent a hysterectomy and radiation therapy for cervical cancer 5 years ago.

• Does she have IBS?• Are there historical clues in this case?• What testing would you do?


Why is Diarrhea Important?

• Diarrhea is common• You will see it!• Affects 1-5% of the adult population

• $$ There can be considerable expense in the work-up/management.

• Cost effective evaluation can be smart

• Differential can be broad• Distinguishing alarm features is critical

4/22/2019

19


Step-Wise Approach to Diarrhea

• 1. Does the patient truly have diarrhea?

• 2. Is the diarrhea really chronic?

• 3. Can you categorize the diarrhea?

• 4. Are there historical clues to the diagnosis?

• 5. Is it diet or medication-induced?

• 6. Is there a factitious component?

Schiller LR, et al. CGH 2017;15:182


Step 1: Does the patient truly have diarrhea?

• Fecal incontinence?

• Overflow from fecal impaction?

• Perception versus reality of volume / frequency?

4/22/2019

20


Definition of diarrhea

• In past, based on volume and time:• >200-250 g (or ml) per day• >4 weeks

• Current way we diagnose:• >3 unformed BM/day• >25% loose or mushy stools• Bristol stool scale 6 or 7


Step 2: Does the patient have acute or chronic diarrhea?

• Acute = 2-4 weeks

• Chronic = >4 weeks

OR

4/22/2019

21


Step 3: Can you categorize the diarrhea?

• Watery• Secretory versus osmotic

• Inflammatory• Bloody stools, abdominal pain, fever, tenesmus

• Fatty• greasy, oily, difficult to flush, floating stools, smelly• Not specific!!!

• Large or small bowel intestine source• Often differs in volume and frequency


Small bowel:large volume, vitamin andmineral deficiencies

Colon:Smaller volume (not always),frequent, bloody, tenesmuswith rectal involvement

4/22/2019

22


Tests Based on Characteristics

• Watery: Secretory versus Osmotic• Osmotic gap = 290 mOsm/kg-2(stool Na+K)

• Gap < 50 Secretory• Gap > 100 Osmotic

• Stool osmolality:• Should be the same as serum

• Lower - urine or water contamination• Higher - stool collection sitting around

e.g. 2(140+ 4)= 288


Osmotic Secretory

Daily volume <1L >1L

Effect of Fast Stops continues

Stool osmolality 290 290

Osmotic gap >100 <50

Common causes Malabsorption*PEG**, lactulose, Mg+ antacids, sorbitol/xylitol

Cholera, toxins,bile acid, VIPoma, gastrinoma, diabetic diarrhea, microscopic colitis, factitious, villous adenoma

*Malabsorption e.g . Fructose, lactose, bacterial overgrowth (SIBO)**PEG = polyethylene glycol

4/22/2019

23


Osmotic Secretory

Testing Strategy

Dietary reviewMalabsorption(breath tests,avoidance, small bowel biopsy)Stool magnesium

CulturesStructural evaluation: colon biopsies.NeuroendocrineVIP, calcitonin, gastrin


Tests based on characteristics

• Inflammatory:• +CRP, fecal calprotectin or lactoferrin

• If positive, these are nonspecific• Differential:

• infection, inflammation, ischemia, radiation

• Often structural evaluation is needed• colonoscopy and/or EGD with biopsies,

enterography

4/22/2019

24


Tests based on characteristics

• Fatty / Steatorrhea• Symptoms: malodorous diarrhea, weight

loss, vitamin ADEK deficiencies• Etiology: pancreatic, mucosal (e.g celiac,

Whipple’s disease)• Tests:

• Qualitative fecal fat (Sudan stain) –’meh’!• Fecal elastase ( pancreatic disease)• Quantitative fecal fat (collection 24-72 hr)

normal < 7g/day or <14 if diarrhea

‘meh’ = low sensitivity/specificity


Step 4: Are There Historical Clues to the Diagnosis?

• Abdominal pain/functional issues - IBS

• Autoimmune, iron deficiency, family history, itchy rash - celiac

• Female, culprit meds - microscopic colitis

• Bariatric surgery (RYGB), radiation, paralytic motility issues - SIBO

• Younger, bloody, fever, family history IBD, extra-intestinal features - IBD

4/22/2019

25


Irritable bowel syndrome (IBS) ROME 4

• Recurrent abdominal pain on average at least 1 day/week in the last 3 months a/w 2 or more features:

• Related to defecation• Change in frequency of stool• Change in form/consistency of stool

• Symptoms present at least 6 months

• In absence of alarm features manage symptoms

Gastroenterology 2016:150:1393


Important in History/Exam

• If ALARM features are present, further workup is needed:

• Bloody stool, weight loss, family history of IBD or bowel cancer, new onset, older age, immunosuppressed

• Keep in mind routine colorectal cancer screening or surveillance based on age and risk factors

4/22/2019

26


Step 5: Does the Patient Have Diet-Induced Diarrhea?

• DIET• Caffeine• Soda, fruit/juice (fructose)• Sweeteners (sucrose)• Sugar free anything (xylitol)• Dairy (lactose)• Wheat (celiac, allergy, sensitivity)• Syrups, elixirs (sorbitol)


Step 5: Does the Patient Have Medication-Induced Diarrhea?

• >700 drugs implicated

• Makes up 7% of medication side effects!

Some to Remember: NSAID

Metformin

Antibiotic

PPI

SSRIs

Mg+

Angiotensin receptor blockers (olmesatan)

Herbal products

Many chemotherapy agents

Rubio-Tapia A, et al. Mayo Clinic Proc 2012;87:732Prieux-Klotz C, et al. Target Oncol 2017;12:301

4/22/2019

27


Step 6: Is there a factitious component?

• Stool osmolality not equal to 290 (diluted)

• Munchausen syndrome

• Melanosis coli• Pigment from stimulant laxative use• Benign/reversible• Up to 15% undergoing diarrhea workup


Evaluation May Include:

Stool Tests

Endoscopy

Imaging

Quantitative Stool Tests

Baseline Labs CBC, TTG, TSH, e-lytes,CRP, vitamin levels

Colonoscopy with TI exam and biopsy,EGD with SB biopy and aspirates

CT enterography, MRE

24-72 hour fat or bile acid collection

Calprotectin, lactoferrin, infectious panel,parasites (Giardia), elastase, c diff, osmol

Very Individualized!

4/22/2019

28


Summary

• Many etiologies for diarrhea can be deciphered from a careful history and examination

• A stepwise approach for diarrhea is cost-effective and efficient.

• #1. Does the patient truly have diarrhea?

• #2. Is it chronic?

• #3. How is it characterized (watery, fatty, inflammatory)

• #4. Historical clues to the diagnosis? (travel, illness, medications)

• #5. Diet or medication induced?

• #6. Could it be factitious?


Thank you!

[email protected]

ibs-d and evaluation of chronic diarrhea · 2019-04-22 · •cost-effective evaluation and...

Documents